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Fertility techniques linked to intellectual disability

A Telethon Kids Institute study showing a link between intellectual disability and some forms of Assisted Reproductive Technology has reinforced the need for co-ordinated long-term monitoring of outcomes of children conceived using these techniques.

The research, published in the journal Pediatrics, found children conceived using Assisted Reproductive Technology (ART) between 1994 to 2002 had only a small increased risk of intellectual disability overall.

However, the risk more than doubled for those born very preterm or using a technique where a single sperm is injected directly into the egg – known as intracytoplasmic sperm injection (ICSI).

Lead researcher Dr Michele Hansen said while the results were important, they needed to be interpreted with caution due to the age of the data available for the study and the fact that technology and procedures in Western Australia had advanced since the study was performed.

“During the study period, the transfer of multiple embryos in a single treatment cycle was the norm in Australia. This practice led to high rates of multiple pregnancies and preterm birth – which are both known to increase the risk of intellectual disability,” Dr Hansen said.

“However, this practice has changed dramatically in Australia over time. As of 2016, 88 per cent of treatment cycles saw only a single embryo transferred, resulting in much lower proportions of multiple and preterm births.”

Dr Hansen said the findings did have important implications for many regions in the world – such as parts of North America, Latin America and the Middle East – where the transfer of multiple embryos in an individual cycle was still the norm.

She said her study also reinforced concerns about ICSI, which was restricted to couples with severe male factor subfertility during the study period, but is now used more broadly.

“Genetic abnormalities occur more frequently in men who are infertile, so ICSI – which bypasses natural selection barriers by injecting a sperm directly into an egg – may allow for the transmission of anomalies to the offspring,” Dr Hansen said.

“ICSI fathers in our study were also older on average and we know that advanced paternal age is associated with a small increased risk of genetic mutations in sperm and genetic disorders in offspring.”

Dr Hansen said her study showed an urgent need for more recent data to try to establish whether the increased risks of intellectual disability are solely related to male subfertility and older paternal age, or if there are other risks associated with the technique itself.

“Until we know more, clinics may consider restricting the use of ICSI to those couples that are unlikely to be able to conceive without it – that is, those with severe male factor subfertility,” Dr Hansen said.

The study included 210,627 live births, of which 1.4% were conceived using ART (1,939 IVF and 937 ICSI births). Read the abstract here.

Key findings:

Children conceived using ART had a small increased risk of intellectual disability overall (1 in 48 ART children were diagnosed vs 1 in 59 for non-ART children)

ICSI-conceived children showed a higher risk of intellectual disability: 1 in 32

The risk of intellectual disability in very preterm births is much greater regardless of method of conception (but within preterm singleton births the risk was doubled for those that were ART-conceived). 1 in 8 ART singletons vs 1 in 14 non-ART singletons born before 32 weeks were diagnosed with intellectual disability.

The risk of severe intellectual disability (IQ<40) is more than doubled for ART births: 1 in 353 ART-conceived children vs 1 in 889 non-ART children were diagnosed with severe intellectual disability.

The research, published as Intellectual Disability in Children Conceived Using Assisted Reproductive Technology, was supported by the National Health and Medical Research Council.

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About Telethon Kids Institute

The Telethon Kids Institute is based within the Perth Children’s Hospital, and is one of the largest, and most successful medical research institutes in Australia, comprising a dedicated and diverse team of more than 700 staff and students.

We've created a bold blueprint that brings together community, researchers, practitioners, policy makers and funders, who share our vision to improve the health and wellbeing of children through excellence in research.

Telethon Kids is independent and not-for-profit. The majority of funding comes from our success in winning national and international competitive research grants. We also receive significant philanthropic support from corporate Australia and the community.